A summary of the research

This study represents an in-depth genetic evaluation of 250 known canine disease variants and genetic diversity within and between dog breeds. To date, this is the most comprehensive dive into the distribution and frequency of known genetic disorders across the domestic dog population. 

To get the results, the team analysed data from more than 1 million dog samples submitted by pet parents or veterinarians and tested on our custom microarray-based panel. The samples included 811,628 mixed breed dogs and 242,665 purebreds from more than 150 countries and territories. 

In our analysis, we found that more than half of the examined dogs–57% to be exact–carry at least one copy of a studied disease-linked variant. We also found that many of the variants are relevant for the health of a dog no matter its breed ancestry. Moreover, we found that some variants always cause disease when present in a dog (meaning that they are fully penetrant) while other variants only lead to signs of a disease in subsets of dogs, or only late in a dog’s life, if at all. 

The team went on to assess genetic diversity levels in over 100 breeds which showed a correlation between the reduction in genetic diversity and an increase in diseases associated with single-gene variants.

The next step in the study was to match the data with potential health impacts. To do this, Wisdom Panel’s team of veterinarians and geneticists talked to pet parents and reviewed electronic medical records of dogs found to be genetically at risk for a disease condition. This allowed our science team to investigate the clinical impact of a number of disease-associated variants in dogs of different breed backgrounds. 

These results shed light on the inheritance of variants across dog breeds and highlight the importance of large-scale population screening studies in improving veterinary diagnostics, breeding programs, and health recommendations for all dogs.

A closer look at the genetic variants

A total of 250 genetic variants were screened during the study - all of which largely follow Mendelian inheritance, meaning they are single genes which follow a certain pattern when passed from parents to offspring. These variants were selected based on previous implications to their involvement in canine inherited disorders. 

Of the total, 207 (roughly 83%) were observed in at least one dog. The majority of disease-associated variants, nearly 88%, were encountered in both mixed-breed and purebred dogs. And, 19 diseases (9%) were exclusive to the mixed-breed population and 6 (nearly 3%) to the purebred population. 

The highest number of screened variants –a total of 8– were found present in two separate mixed-breed dogs. And, when looking at a subset of 242 tested disease-associated variants, at least one copy of a variant was found in 57% of the dogs tested.

Heterozygosity and diversity scoring

Heterozygosity, also known as genetic diversity, is a representation of the commonality within a range of inherited genes from each side of the family. Dogs that are more heterozygous have received a higher number of diverse genes from their father and mother. In contrast, dogs that are more homozygous inherited more of the same genes from their father and mother. In short, heterozygous means having different variants of a gene while homozygous means having the same gene variants. Therefore, dogs that are more heterozygous are more genetically diverse.

In previous studies, we’ve shown that a higher proportion of mixed-breed dogs will be heterozygous for at least one of 9 examined recessive disease variants compared with purebred dogs, while a higher proportion of purebred dogs will be homozygous for at least one of the same recessive disease variants compared with mixed-breed dogs. In this new study, we sought to further refine understanding of this pattern. To do this, we leveraged the availability of heterozygosity estimates provided as part of the genetic testing for dogs within the study. And, as expected, we found that purebred dogs had a lower mid-range value than mixed-breed dogs, indicating a higher level of genetic inbreeding in purebreds. Following this finding, the two groups of dogs were considered separately in data analysis.

The correlation between genetic diversity levels and presence of disease variants was also examined. And it was found that increased heterozygosity weakly matched with an increased number of disease variants, present at 1 copy, in both mixed and purebred dogs. More notably, the team found that a decrease in heterozygosity paired with an increased number of disease variants with 2 copies. This pattern was  observed in both dogs classified as mixed-breed and purebred, and persisted when the analysis was repeated including only the recessive disease variants.

Frequency of genetic disorders

The top 20% of the most prevalent disease variants accounted for 98% of all disease-associated variants observed in the study sample. Additionally, the distribution was highly similar across both the mixed-breed and purebred dog groups. (Only 7 of the 50 most common variants in mixed-breed dogs were not present among the purebred top 50 variants, and vice versa.) 

In this study, we were able to better characterize variant findings not previously documented in the scientific literature in specific purebreds. Based on genetically at-risk dogs showing at least some clinical signs that are associated with the disease in question, we found evidence for clinical relevance in the following: 

• Cystinuria in the French Bulldog
• Factor VII deficiency in the Basset Hound
• Hypocatalasia in the Basset Hound
• Macrothrombocytopenia in the Chesapeake Bay Retriever
• Multidrug resistance 1 (MDR1) related medication sensitivity in the Siberian Husky
• Von Willebrand’s Disease Type 1 (vWD 1) in the Boston Terrier, Cairn Terrier, Pomeranian, and Pug.

Additionally, we found evidence suggesting that the specific variants previously associated with the following conditions have high or complete penetrance across breed ancestry backgrounds:

• Canine leukocyte adhesion deficiency type III
• Chondrodysplasia
• Hypocatalasia
• Factor VII deficiency
• Cone-rod dystrophy 2
• Spinocerebellar ataxia
• Two types of ichthyoses
• Focal non-epidermolytic palmoplantar keratoderma
• Hemophilia A
• Hereditary footpad hyperkeratosis
• Neuroaxonal dystrophy
• Skeletal dysplasia 2
• Trapped neutrophil syndrome

In other words, these findings suggest that these variants are always clinically relevant when present in a dog.

The road ahead

This study demonstrates the usefulness of genetic panel testing in veterinary care and its importance in supporting breeding programs as well as the general dog community. But our effort to further our understanding of canine genetic epidemiology doesn’t end here!. As more dogs are genetically tested and our research continues, we will learn more about variant heritage in the broader domestic dog population–beyond just breeds. Why is this important? Because genetic testing, regardless of the breed or population background, helps raise awareness of various inherited single gene conditions in dogs and provides information that pet parents can share with their veterinarians. Our goal is to decipher the genetics of common complex canine diseases and enable more personalized, precise healthcare for all dogs.

Our team would like to thank all pet owners and breeders who have supported research by submitting samples from their dogs for genetic testing and openly sharing information about their dogs’ health, wellbeing, and conformation. Additionally, we’d like to thank the Banfield Pet Hospital clinicians who diligently and consistently recorded their observations in medical records. We also wish to extend a special thanks to all our research colleagues and peers, whose dedication to the discovery of genetic variants underlying canine disease has made studies like ours possible.